Flavone derivative and medicine comprising the same

Abstract

This invention relates to a flavone derivative represented by the formula (1) or a salt thereof, and also to a medicine containing the same. ##STR1## wherein A represents H, halogen, phenyl, naphthyl, a group of the formula (2) in which X is H or halogen, B is --CH═CH--, --CH═N--, --N(R 7 )-- (R 7 : lower alkyl or alkoxyalkyl), --O-- or --S--; W represents a single bond, --CH 2 O-- or --CH═CH--; at least one of R 1 to R 4 represents --COOH, --CN, alkyloxycarbonyl, tetrazolyl or --CONHR 8 (R 8 : H, lower alkyl or phenylsulfonyl), the remainder thereof individually represent H, halogen, --OH, lower alkyl or lower alkoxyl; R 5 represents H, --OH, lower alkoxyl, --O(CH 2 ) m NR 9 R 10 (R 9 ,R 10 : H or lower alkyl, or coupled together with the adjacent N to form a phthalimido group; m: 1-5), or a group of the formula (3) (n: 1-5, l: 2-3; and R 6 represents H, halogen, lower alkyl or lower alkoxyl. A situation where A is H or halogen, W is a single bond and R 5 is H is excluded. The compound (1) has excellent cys-LT 1 receptor antagonism.

What is claimed is: 
     
       1. A flavone derivative represented by the following formula (1): ##STR70## wherein A represents a hydrogen atom, a halogen atom, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, or a group represented by the following formula (2): ##STR71## wherein X represents a hydrogen atom or a halogen atom, and B represents --CH═CH--, --CH--N--, --N(R 7 )-- in which R 7  represents a lower alkyl group or an alkoxyalkyl group, --O-- or --S--, W represents a single bond, --CH 2  O-- or --CH═CH--,   at least one of R 1 , R 2 , R 3  and R 4  represents a carboxyl group, a cyano group, a substituted or unsubstituted alkyloxycarbonyl group, a tetrazolyl group, or --CONHR 8  in which R 8  represents a hydrogen atom, a lower alkyl group or a phenylsulfonyl group, and the remainder thereof may be the same or different and individually represent a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxyl group,   R 5  represents a hydrogen atom, a hydroxyl group, a substituted or unsubstituted lower alkoxyl group, --O(CH 2 ) m  NR 9  R 10  in which R 9  and R 10  may be the same or different and individually represent a hydrogen atom or a lower alkyl group or are coupled together with the adjacent nitrogen atom to form a phthalimido group, and m stands for a number of 1-5, or a group represented by the following formula (3): ##STR72## wherein n stands for a number of 1-5, l stands for a number of 2-3, and B and X have the same meanings as defined above, and   R 6  represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxyl group, with the proviso that a situation where A is a hydrogen atom or a halogen atom, W is a single bond and R 5  is a hydrogen atom is excluded; or   a salt of said flavone derivative.   
     
     
       2. The compound of claim 1, wherein in the formula (1), A represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, or a group represented by the following formula (2): ##STR73## wherein X represents a hydrogen atom or a halogen atom, and B represents --CH═CH--, --CH--N--, --N(R 7 )-- in which R 7  represents a lower alkyl group or an alkoxyalkyl group, --O-- or --S--,   W represents --CH 2  O-- or --CH═CH--,   at least one of R 1 , R 2 , R 3  and R 4  represents a carboxyl group, a cyano group, a substituted or unsubstituted alkyloxycarbonyl group, a tetrazolyl group, or --CONHR 8  in which R 8  represents a hydrogen atom, a lower alkyl group or a phenylsulfonyl group, and the remainder thereof may be the same or different and individually represent a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxyl group,   R 5  represents a hydrogen atom, a hydroxyl group, a substituted or unsubstituted lower alkoxyl group, --O(CH 2 ) m  NR 9  R 10  in which R 9  and R 10  may be the same or different and individually represent a hydrogen atom or a lower alkyl group or are coupled together with the adjacent nitrogen atom to form a phthalimido group, and m stands for a number of 1-5, or a group represented by the following formula (3): ##STR74## wherein n stands for a number of 1-5, l stands for a number of 2-3, and B and X have the same meanings as defined above, and   R 6  represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxyl group.   
     
     
       3. The compound of claim 1, wherein in the formula (1), A represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, or a group represented by the following formula (2): ##STR75## wherein X represents a hydrogen atom or a halogen atom, and B represents --CH═CH--, --CH--N--, --N(R 7 )-- in which R 7  represents a lower alkyl group or an alkoxyalkyl group, --O-- or --S--,   W represents --CH 2  O-- or --CH═CH--,   at least one of R 1 , R 2 , R 3  and R 4  represents a carboxyl group, a cyano group, a substituted or unsubstituted alkyloxycarbonyl group, a tetrazolyl group, or --CONHR 8  in which R 8  represents a hydrogen atom, a lower alkyl group or a phenylsulfonyl group, and the remainder thereof may be the same or different and individually represent a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxyl group,   R 5  represents a hydrogen atom, a hydroxyl group, a substituted or unsubstituted lower alkoxyl group, or --O(CH 2 ) m  NR 9  R 10  in which R 9  and R 10  may be the same or different and individually represent a hydrogen atom or a lower alkyl group or are coupled together with the adjacent nitrogen atom to form a phthalimido group, and m stands for a number of 1-5, and   R 6  represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxyl group.   
     
     
       4. The compound of claim 1, wherein in the formula (1), A represents a hydrogen atom or a halogen atom,   W represents a single bond,   at least one of R 1 , R 2 , R 3  and R 4  represents a carboxyl group, a cyano group, a substituted or unsubstituted alkyloxycarbonyl group, a tetrazolyl group, or --CONHR 8  in which R 8  represents a hydrogen atom, a lower alkyl group or a phenylsulfonyl group, and the remainder thereof may be the same or different and individually represent a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxyl group,   R 5  represents a hydroxyl group, a substituted or unsubstituted lower alkoxyl group, --O(CH 2 ) m  NR 9  R 10  in which R 9  and R 10  may be the same or different and individually represent a hydrogen atom or a lower alkyl group or are coupled together with the adjacent nitrogen atom to form a phthalimido group, and m stands for a number of 1-5, or a group represented by the following formula (3): ##STR76## wherein n stands for a number of 1-5, l stands for a number of 2-3, and B and X have the same meanings as defined above, and   R 6  represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxyl group.   
     
     
       5. A medicine comprising as an effective ingredient the compound of any one of claims 1-4. 
     
     
       6. The medicine of claim 5, which is a cys-LT 1  receptor antagonist. 
     
     
       7. The medicine of claim 5, which is a preventive or therapeutic for an allergic disease. 
     
     
       8. The medicine of claim 5, which is a preventive or therapeutic for a disease selected from asthma, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, urticaria, psoriasis, rheumatism, inflammatory colitis, cerebral ischemia or cerebral apoplexy. 
     
     
       9. A medicinal composition comprising the compound of any one of claims 1-4 and a pharmacologically acceptable carrier. 
     
     
       10. A treatment method of an allergic disease, which comprises administering an effective amount of the compound of claim 1. 
     
     
       11. The treatment method of claim 10, wherein said allergic disease is a disease selected from asthma, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, urticaria, psoriasis, rheumatism, inflammatory colitis, cerebral ischemia or cerebral apoplexy.